DESCRIPTION (Adapted from the applicant abstract): This new R01 application, currently in its 4th version seeks to understand the cellular and molecular mechanisms of human benign prostatic hyperplasia. The central hypothesis is that the growth and differentiation of the prostate is regulated by mesenchyme-epithelial interactions mediated by the local production and action of peptide growth factors such as TGFa, TGFB and KGF. Two specific aims are planned to test this hypothesis. The first aim is to characterize a human cell line (BPH-1) that was generated by SV-40 large T antigen transformation of epithelial cells obtained from a BPH specimen. The characterization of these cells will include the testing for the expression of cytokeratins, androgen receptor, and prostate-specific secretory proteins. In addition, the effects of various growth factors on this cell line and the regulation of growth factor production by androgens will also be studied. The second aim is to investigate the role of mesenchyme-epithelial interaction in the regulation of the growth and development of the prostate. Tissue recombinants will be grown in athymic nude mice. Growth kinetics, tissue morphology and the expression of markers of prostatic differentiation as well as growth factor expression will be studied.